Full Heparinization Research Articles

Surgical Management of Thromboembolic Complications Associated with Mitral Valve Stenosis

Major systemic thromboembolism accounts for 40% of deaths in individuals with mitral valve stenosis (MS). Furthermore, atrial fibrillation (AF) occurs in approximately 45% of patients with MS, adding to the burden of disease. Contraindications to the use of oral anticoagulation such as recent intracranial haemorrhage, places patients at high risk of thromboembolic events. We present the case of a 70-year-old female who presented with symptoms of acute bilateral lower limb and spinal cord ischaemia, within 24 hours of discharge from a stroke rehabilitation unit. Her initial admission was following an atraumatic intracranial haemorrhage after the administration of warfarin as thrombo-prophylaxis for AF. Following surgery for haematoma evacuation, her anticoagulation had been completely ceased. A computed tomography angiogram of her chest demonstrated a saddle embolism of her descending aorta at the bifurcation of the common iliac arteries, and a filling defect in the left atrial appendage. She underwent emergent bilateral aorto-iliac thrombectomy and postoperative anticoagulation with intravenous heparin. Transoesophageal echocardiography showed a 4.5 × 2.2 cm mobile left atrial thrombus and moderate rheumatic MS and she underwent left atrial thrombectomy and mitral valvotomy with full heparinisation and cardiopulmonary bypass. Her postoperative recovery was unremarkable and she was re-commenced on warfarin. This case demonstrates the potentially devastating thromboembolic complications of AF and MS, and the difficulties in decision-making in regards to anticoagulation for patients with previous bleeding complications. Warfarin remains the only oral anticoagulant suitable for these patients given its potential reversibility and titratable dosing regime.

A Retrospective Study of Venous Thromboembolism in Acute Leukemia Patients during Prolonged Hospital Stay. the Princess Margaret Cancer Centre Experience

▪BackgroundThe role of thromboprophylaxis in solid organ malignancies is well established. Hematologic malignancies can also be associated with a considerable risk of thromboembolic complications. The incidence of these events is variable and is influenced by multiple factors. Limited data are available regarding the incidence of venous thromboembolism (VTE) in hospitalized acute leukemia (AL) patients. The management of symptomatic VTE in patients with AL can be challenging due to the increased risk of thrombocytopenia-related bleeding.MethodsThe Discharge summary Database (DAD) was used to extract post-admitted PE and DVT volumes in AL patients admitted to Princess Margaret Cancer Centre from 2007-2016. ICD-10-CA diagnosis codes for acute leukemia, and both PE and DVT events, were used. Only patients diagnosed with VTE at least 48 hours post-admission were included to restrict the cohort to patients that developed VTE during their admission.ResultsWe analyzed a total of 10,041 patients that were admitted to Princess Margaret Cancer Centre during the 2007-2016 period. (Table 1) Of these, 7759 had a solid tumor diagnosis (271 VTE events, 3.4%) and 2282 patients had AL (1675 AML, 464 ALL, 144 APL). The AL patients (AML, ALL, APL) admitted to our Centre for chemotherapy or for the management of complications were further evaluated to determine VTE incidence and to evaluate its management in this setting. As of September 2012, patients with solid tumors treated at our Centre received standard thromboprophylaxis as part of an institutional in-patient (VTE) prophylaxis policy (IPP) that reduced the incidence of VTE from 4.8% (219/4520) to 1.6% (3239/52) before and after the policy was initiated, respectively. AL patients are not given prophylactic anticoagulation. 37 AL patients (22 AML, 10 ALL, and 5 APL; overall incidence 1.6%) developed symptomatic VTE (DVT only 23, PE only 8, DVT + PE 6). VTE was reported as central venous catheter related in 12/37 patients (32.4%). PE was detected in all cases by CT-PE. Median age of VTE patients was 53 years (range 32-77), with a median hospital stay of 35 days (range 2-144). Chemotherapy was given to 26 of the 37 patients that developed VTE, with 20 receiving initial induction chemotherapy. 17/37 (46%) patients had PLT<50.000/mm3 at VTE diagnosis. Full dose low molecular weight heparin with platelet transfusion support was used to treat 35/37 patients with acute VTE during the first month of treatment. 2/37 did not receive anticoagulation due to ongoing active bleeding. None of the treated patients experienced major bleeding.ConclusionsIn our experience, the incidence of VTE in AL patients during prolonged hospital stay is relatively low, raising questions about the need for routine VTE prophylaxis in this group. The relatively increased risk of VTE in AL patients receiving chemotherapy (particularly, induction chemotherapy), should prompt particular scrutiny in symptomatic patients. [Display omitted] DisclosuresSchuh:Amgen: Membership on an entity's Board of Directors or advisory committees. Yee:Novartis Canada: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gupta:Incyte Corporation: Consultancy, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Schimmer:Novartis: Honoraria.

Apical closure device for transapical valve procedures.

Transapical transcatheter valve procedures are performed through a left minithoracotomy and require apical sutures to seal the apical access site. The use of large-calibre devices compromises any attempt to fully perform the procedure with a thoracoscopic approach or percutaneously. We report our preliminary experience in animals with a new sutureless self-expandable apical occluder, engineered to perform transapical access site closure in a minimally invasive setting with large-size introducer sheaths. The apical occluder with extendable waist was implanted in six young pigs during an acute animal study. Under general anaesthesia, animals (mean weight: 62 ± 8 kg) received full heparinization (heparin: 100 UI/kg; activated clotting time above 250 s). Through a median sternotomy, a 21-Fr Certitude™ introducer sheath (outer diameter: 25 Fr) was placed over the wire into the cardiac apex. The delivery catheter carrying the constrained apical plug was inserted into the sheath and deployed under fluoroscopic control, whereas the Certitude™ was retrieved. After protamine infusion, we observed and recorded the 1-h bleeding with standard haemodynamic parameters. Animals were sacrificed, and hearts analysed. Six apical closure devices were successfully introduced and deployed in six pig hearts through large-size apical sheaths at first attempt. In all animals, the plugs guaranteed immediate apical sealing and traces of blood were collected in the pericardium during the 1-h observational period (mean of 16 ± 3.4 ml of blood loss per animal). Haemodynamic parameters remained stable during the entire study period and no plug dislodgement was detected with normal systemic blood pressure (mean arterial mean blood pressure: 65 ± 7 mmHg). Post-mortem analysis confirmed the full deployment and good fixation of all plugs, without macroscopic damages to the surrounding myocardium. This sutureless self-expandable apical occluder is a simple device capable of sealing large-size apical access sites (20-35 Fr) in an acute animal study. This approach is a step further towards less invasive transapical valve procedures in the clinical setting, and further animal tests will be performed to confirm the long-term efficacy and safety of this device.

U-Shape Kissing Chimney Thoracic Endovascular Aneurysm Repair for a Traumatic Arch Rupture in a Polytraumatized Patient.

An 18-year-old male patient was admitted to our hospital because of a high impact trauma. A computed tomography scan showed massive mediastinal bleeding due to a posteriorly located rupture of the aortic arch with formation of a pseudoaneurysm. Although urgent repair was indicated, open cardiac surgery was not feasible, as this would involve full heparinization in a patient with subarachnoid bleeding. The chosen solution was to perform a percutaneous thoracic endovascular aneurysm repair (TEVAR) and a kissing chimney procedure using a U-shape configuration.

Endovascular cooling catheter related thrombosis in patients undergoing therapeutic hypothermia for out of hospital cardiac arrest

BackgroundTherapeutic hypothermia improves neurologic outcome and survival in patients following out-of-hospital cardiac arrest (OHCA). Endovascular cooling devices are commonly used to rapidly achieve and maintain hypothermia. The use of these devices may be associated with catheter related thrombosis. The objective of this study was to determine the risk of catheter related thrombosis associated with the use of an endovascular cooling catheter in patients referred for therapeutic hypothermia following OHCA. Methods and resultsWe conducted a retrospective cohort study on consecutive patients, referred for therapeutic hypothermia following OHCA, between February 2012 and May 2013. Of 80 patients initially treated with therapeutic hypothermia, 61 completed the cooling protocol using an endovascular cooling device. The primary outcome was catheter related thrombosis defined as evidence of thrombus in the inferior vena cava, deep vein thrombosis or pulmonary embolism during the index hospitalization. We further evaluated the incidence of the primary outcome between patients on dose adjusted intravenous unfractionated heparin compared to those on a subcutaneous prophylactic regimen alone. Catheter related thrombosis was observed in 9/61 (14.7%), with nine events in the prophylaxis group compared to none in the full dose unfractionated heparin group (22.0% vs. 0.0%, p=0.02). ConclusionsThe use of endovascular catheters for induction of therapeutic hypothermia is associated with a high rate of catheter related thrombosis. This risk appears to be abrogated with dose adjusted unfractionated heparin infusion.

Anex vivoevaluation of blood coagulation and thromboresistance of two extracorporeal circuit coatings with reduced and full heparin dose

Bioactive Carmeda® heparin-coated extracorporeal circuits (ECCs) have been shown to reduce contact phase and coagulation activation during cardiopulmonary bypass (CPB). Heparin coating is therefore effective in safely reducing coagulation during routine CPB. Balance® Biosurface is a new, recently developed biopassive coating containing negatively charged sulphonated polymers. This study sought to compare the clotting activation and thromboresistance of the Balance® (B) circuit with that of the Carmeda® (C) with full-dose systemic heparin (FDH) and reduced-dose systemic heparin (RDH). This ex vivo study set-up comprising 40 experiments consisted of simplified ECC and circulation of freshly donated human blood. RDH and FDH regimens were obtained with 0.5 IU/ml and 1 IU/ml heparin administered to reach target activated clotting times (ACTs) of 250 and 500 s, respectively. The study design comprised four groups: FDH-C, FDH-B, RDH-C and RDH-B (all n = 10). Blood was sampled prior to and during the 2-h CPB. Coagulation activation was assessed (FXIIa, F1.2) and electron microscope scan imaging of oxygenators enabled determination of adhesion scores. With a biopassive compared with bioactive surface, mean ACT was lower, regardless of the heparin regimen applied (P < 0.001), whereas the total heparin dose required to maintain ACT was above target level (P < 0.001). However, FXIIa and F1.2 values were similar in all groups throughout, as were pressure gradients among oxygenators. All groups demonstrated similar adhesion scores following ultrastructural oxygenator assessment. In the absence of surgical-related haemostatic disturbances and based on target ACT levels under reduced- or full-dose heparin, the clotting process was similar to heparin-coated and new sulphonated polymer-coated ECC, both demonstrating similar thromboresistance.

Characterization of interactions between heparin/glycosaminoglycan and adeno-associated virus.

Adeno-associated virus (AAV) is a key candidate in the development of gene therapy. In this work, we used surface plasmon resonance spectroscopy to study the interaction between AAV and heparin and other glycosaminoglycans (GAGs). Surface plasmon resonance results revealed that heparin binds to AAV with an extremely high affinity. Solution competition studies showed that binding of AAV to heparin is chain length-dependent. AAV prefers to bind full chain heparin. All sulfo groups (especially N-sulfo and 6-O-sulfo groups) on heparin are important for the AAV-heparin interaction. Higher levels of sulfo group substitution in GAGs enhance their binding affinities. Atomic force microscopy was also performed to image AAV-2 in a complex with heparin.

Therapeutic Anticoagulation After Craniotomies: Is the Risk for Secondary Hemorrhage Overestimated?

Deep venous thrombosis (DVT) and pulmonary embolism (PE) are major causes of postoperative morbidity and mortality in surgery. However, there is neither a standardized protocol for perioperative prevention of DVT or PE in neurosurgery nor a consensus concerning the management of postoperative DVT or PE after craniotomy in the early postoperative course. We retrospectively analyzed management and complications in a group of patients with postoperative DVT or PE after craniotomy between 2006 and 2011 to estimate the risk of secondary hemorrhage under therapeutic anticoagulation. The interval between time of craniotomy and diagnosis of PE or DVT, administered anticoagulation, and the appearance of a clinically relevant secondary hemorrhage were analyzed. Forty-two patients met the given criteria. Indications for surgery were intracranial tumors (n = 33), aneurysms (n = 5), and hematomas (n = 4). PE or DVT was observed between the first and the 28th postoperative day (median, fifth postoperative day). Therapeutic anticoagulation was performed with enoxaparin or heparin (according to partial thromboplastin time levels). Full heparinization was applied in 30 patients between the second and the 30th postoperative day (median, 12th postoperative day). None of these patients developed a secondary hemorrhage. The documented differences in the anticoagulative drug used, the drug's dosage, and the start of medication reflect the lack of a standardized protocol concerning the treatment of postoperative PE or DVT after craniotomy. A more aggressive management regarding the application of anticoagulative drugs after craniotomy may be justified considering the absence of clinically relevant hemorrhages in this study and the life-threatening potential of perioperative DVT or PE.

Venenthromboseembolieprophylaxe bei urologischen Operationen

Deep vein thrombosis and the associated danger of pulmonary embolism are two manifestations of one disease. The frequency of deep vein thrombosis in operative medicine without medicinal prophylaxis varies between 14% and 32% and the resulting pulmonary embolism rate is approximately 0.8-6.2%. When deep vein thrombosis is suspected, a diagnostic clarification is carried out by determination of D-dimer levels, compression sonography of the veins and if necessary phlebography. When pulmonary embolism is suspected, the diagnostics are extended to computed tomography angiography (CTA) and if necessary echocardiography. If deep vein thrombosis and/or pulmonary embolism are present, therapy must be started immediately (full heparinization or systemic thrombolysis). The occurrence of deep vein thrombosis with subsequent pulmonary embolism can be reduced by consistent prophylaxis. The risk assessment incorporates exponential and dispositional risk factors. Prophylactic measures include early mobilization, compression stockings and in the highest risk group (radical prostatectomy and cystectomy) medicinal measures, as a rule low molecular weight heparins. Venous thromboembolism prophylaxis following such interventions should be continued postoperatively for 4-5 weeks.

Preoperative Angiotensin System Inhibitor Use Attenuates Heparin-Induced Hypotension in Patients Undergoing Cardiac Surgery

Both angiotensin system inhibitor (ASI) use and heparin are associated with hypotension. This study attempted to determine whether preoperative ASI therapy affected the hemodynamic response to heparin administered to patients undergoing cardiac surgery. Sixty-two patients undergoing elective cardiac surgery requiring full (300 units/kg) systemic heparinization were studied prospectively. Thirty-three patients were receiving preoperative ASI therapy, whereas 29 patients were not. Anesthetic technique and mechanical ventilation parameters were standardized. Hemodynamics were recorded at 3 time points: baseline (just before the administration of heparin), 1-minute post-heparin administration, and 4-minute post-heparin administration. Single university hospital. Patients undergoing elective cardiac surgery. None. The 2 groups were similar regarding preoperative demographics and baseline hemodynamics. Baseline mean arterial pressure (MAP) in non-ASI patients was 82.0 mmHg, and it decreased significantly to 76.3 mmHg (1 min; p<0.05) and 70.7 mmHg (4 min; p<0.05) following heparin administration. MAP values in ASI patients were 81.9 mmHg, 81.8 mmHg, and 76.8 mmHg at baseline, 1-minute post-heparin, and 4-minute post-heparin administration, respectively (changes not significant).Within-group analysis revealed that non-ASI patients experienced significant decrease in MAP at 1-minute (-6.6%, p = 0.01) and 4-minute (-13.0%, p = 0.0011) post-heparin administration, whereas ASI patients did not (+1.9%, p = 0.52; -3.8%, p = 0.16, respectively). Between-group analysis revealed that differences in MAP values at 1 minute were significant (p = 0.03), whereas differences at 4 minutes were not significant (p = 0.05). This prospective clinical study indicated that preoperative ASI therapy until the day before surgery may attenuate heparin-induced hypotension. Definitive mechanistic insight requires further clinical study.

Evidence-Basis for Anticoagulants for Cerebral Sinus Venous Thrombosis?

HomeStrokeVol. 44, No. 6Evidence-Basis for Anticoagulants for Cerebral Sinus Venous Thrombosis? Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBEvidence-Basis for Anticoagulants for Cerebral Sinus Venous Thrombosis? David K. Cundiff, MD David K. CundiffDavid K. Cundiff Long Beach, CA Search for more papers by this author Originally published16 Apr 2013https://doi.org/10.1161/STROKEAHA.113.000987Stroke. 2013;44:e67Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2013: Previous Version 1 To the Editor:The recent case of cerebral sinus venous thrombosis (CSVT) in the US Secretary of State Hillary Clinton brought my attention to articles that lay out the evidence-basis for the use of full dose heparin and oral anticoagulant drugs for CSVT. Unfortunately, articles published in Stroke by investigators from the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT), a large prospective observational study, have failed to report important evidence against the hypothesis that anticoagulants reduce morbidity and mortality of patients with CSVT. The following points have been missed specifically:1. Canhão et al1 did not report the odds ratios of heparinized versus nonanticoagulated patients regarding survival at discharge and at last follow-up, new central nervous system bleeding during hospitalization, and other clinical outcomes.2. Although Canhão and other ISCVT investigators reported the heparinization status of 27 out of 624 patients who died in the study (25 out of 27 deaths were in heparinized patients), they did not report the number of patients given and not given full dose heparin or if any nonheparinized patients were diagnosed at autopsy. Apparently, 1 of 2 nonheparinized patients that died was diagnosed at autopsy, so no clinical decision was made not to anticoagulate. Consequently, readers could not know whether heparin was associated with good or bad outcomes.3. Coutinho et al2 used the same ISCVT database to make the case for recommending low molecular weight heparin instead of unfractionated heparin in CSVT patients. Fortunately, given the nature of the low molecular weight heparin versus unfractionated heparin comparison, this article had to reveal the number of nonanticoagulated and heparinized patients (104 versus 520).4. I calculated the odds ratio for mortality in heparinized versus nonanticoagulated full dose patients (excluding the patient diagnosed at autopsy) using data from the above 2 ISCVT articles (odds ratio, 5.15; 95% confidence interval, 0.69-38.5; P=0.08).1,2 This indicates a strong trend toward heparin increasing mortality. I could not calculate the odds ratios regarding anticoagulation for the other clinical outcomes because data were not available.5. Of interest regarding the Hillary Clinton case was that, for ISCVT patients ≥65 years old, 49% died or became dependent by 6 months versus 9% for patients <65 years old.3 Hillary Clinton is 65 years old. Of 46 patients ≥65 years old alive at discharge from the hospital, 2 (4.3%) patients later died of hemorrhage (1 hemorrhagic stroke and 1 systemic hemorrhage), while still taking oral anticoagulants.3Coutinho et al4,5 presented the evidence-basis for heparin and oral anticoagulants for CSVT in a Cochrane Review and in Stroke. This meta-analysis of 2 small randomized controlled trials reported a non-significant risk ratio (RR) for death (risk ratio, 0.33; 95% confidence interval, 0.08–1.28).4,5 However, the death rate in the placebo group of these small trials conducted in the 1980s and 1990s was almost about 18x higher than in nonanticoagulated patients from the larger and more recent ISCVT (17.9% [7 out of 39 patients] versus 0.96% [1 (excluding the autopsy diagnosed patient) out of 104 patients]). More frequent and better diagnostic imaging has increased the incidence of CSVT, including much milder cases. Better supportive care may have also improved outcomes.The ISCVT authors should present all of the clinical outcome comparisons in anticoagulated versus nonanticoagulated patients and explain why they should or should not withdraw their case for anticoagulant treatment for patients with CSVT.David K. Cundiff, MDLong Beach, CADisclosuresNone.FootnotesStroke welcomes Letters to the Editor and will publish them, if suitable, as space permits. Letters must reference a Stroke published-ahead-of-print article or an article printed within the past 3 weeks. The maximum length is 750 words including no more than 5 references and 3 authors. Please submit letters typed double-spaced. Letters may be shortened or edited. Include a completed copyright transfer agreement form (available online at http://stroke.ahajournals.org and http://submit-stroke.ahajournals.org).

Structural Studies of the Interaction of Crataeva tapia Bark Protein with Heparin and Other Glycosaminoglycans

CrataBL, a protein isolated from Crataeva tapia bark, which is both a serine protease inhibitor and a lectin, has been previously shown to exhibit a number of interesting biological properties, including anti-inflammatory, analgesic, antitumor, and insecticidal activities. Using a glycan array, we have now shown that only sulfated carbohydrates are effectively bound by CrataBL. Because this protein was recently shown to delay clot formation by impairing the intrinsic pathway of the coagulation cascade, we considered that its natural ligand might be heparin. Heparin is a glycosaminoglycan (GAG) that interacts with a number of proteins, including thrombin and antithrombin III, which have a critical, essential pharmacological role in regulating blood coagulation. We have thus employed surface plasmon resonance to improve our understanding of the binding interaction between the heparin polysaccharide and CrataBL. Kinetic analysis shows that CrataBL displays strong heparin binding affinity (KD = 49 nM). Competition studies using different size heparin-derived oligosaccharides showed that the binding of CrataBL to heparin is chain length-dependent. Full chain heparin with 40 saccharides or large oligosaccharides, having 16-18 saccharide residues, show strong binding affinity for CrataBL. Heparin-derived disaccharides through tetradecasaccharides show considerably lower binding affinity. Other highly sulfated GAGs, including chondroitin sulfate E and dermatan 4,6-disulfate, showed CrataBL binding affinity comparable to that of heparin. Less highly sulfated GAGs, heparan sulfate, chondroitin sulfate A and C, and dermatan sulfate displayed modest binding affinity as did chondroitin sulfate D. Studies using chemically modified heparin show that N-sulfo and 6-O-sulfo groups on heparin are essential for CrataBL-heparin interaction.

Aprotinin Reduces the Procalcitonin Rise Associated With Complex Cardiac Surgery and Cardiopulmonary Bypass

Aprotinin, a nonspecific serine protease inhibitor, has been primarily used as a haemostatic drug in cardiac surgery with cardio-pulmonary bypass (CPB). This study investigated the effect of aprotinin on the post-operative levels of procalcitonin (PCT) and a set of cytokines in patients undergoing pulmonary artery endarterectomy (PEA). We analyzed 60 patients with chronic thromboembolic pulmonary hypertension undergoing PEA. 30 patients (Group A) were treated with aprotinin (2,00,00 IU prior anesthesia, then 2,00,00 IU in CPB prime and 50,00 IU per hour continuously); a further 30 patients (Group B) received tranexamic Acid (1 g before anesthesia, 1 g after full heparin dose and 2 g in CPB prime). PCT, TNFalpha, IL-1beta, IL-6, and IL-8 arterial concentrations were measured from before until 72 hours after surgery. Aprotinin significantly affected early post-PEA plasma PCT. Patients treated with aprotinin (Group A) had lower peak PCT levels compared to patients in Group B (1.52 ng/ml versus 2.18, p=0.024). Postoperative peak values of PCT and IL-6 correlated closely in both groups (r=0.78, r=0.83 respectively). Aprotinin attenuates the post-PEA increase of PCT in the same manner as other pro-inflammatory cytokines. Significant correlation between PCT and IL-6 post-surgery may be indicative of an indirect IL-6-mediated pathway of PCT alteration.

Weaning from cardiopulmonary bypass

The main goal of weaning from cardiopulmonary bypass (CPB) is a smooth transition from mechanical pump-assisted circulation to spontaneous heart activities with sufficient blood flow to maintain systemic circulation. Before initiation of weaning from the CPB, optimal condition for re-beating should be prepared. Normothermia (core temperature > 36℃) is achieved by actively re-warming through the CPB heat exchanger, active warming devices. However, core temperature should not be exceeded by more than 38℃ to avoid postoperative neurological dysfunction [1]. The findings of laboratory data should be within normal ranges. Arterial blood gas analysis is carried out to identify oxygen content of the blood as hematocrit (> 25%), hemoglobin (> 7 g/dl), PaO2 (> 100 mmHg) and absence of metabolic, electrolytic disturbances. The anesthesiologists restart sleeping alarms and adjust monitors, ventilator settings and oxygen flows. After aortic declamping, heart re-beat spontaneously in most cases with minor supportive interventions such as electrical defibrillation, pace maker, and small dose of inotropics. Atrial kick contributes more than 20% of ventricular filling, returning and maintaining of normal sinus rhythm (heart rate between 70-100 beats per min) is preferable. Electric conversion of supraventricular tachycardia, atrial fibrillation and temporary cardiac pacing for atrioventricular conduction block should be considered. Optimized preload is achieved by volume control, mean arterial pressure maintained within 70-90 mmHg with vasoactive agents. In case of inability to wean from CPB despite preload optimization, global cardiac function and completeness of surgery should be assessed by transesophageal echocardiography (TEE) examination. Most common causes of weaning difficulty are left and/or right ventricular failures and inappropriate vasodilatation. TEE allows diagnostic and therapeutic decision makings, and appropriate treatment option. Routine TEE examinations before terminating the CPB is essential for detecting unexpected problems such as an iatrogenic aortic dissection from arterial cannulation site or intracardiac thrombus formations even after full heparinization or any other anatomical anomalies [2,3]. Because of major complication of TEE probe insertion is the esophageal injury, anesthesiologists carefully manipulate TEE probe, especially patient with an esophageal pathology preoperatively [4]. Faultiness of surgery should be excluded (valvular dysfunction, coronary graft failure, left ventricular outflow obstruction) by TEE examinations, and vasoplegic syndrome managed by vasopressor administration [5]. The recently emerged minimally-invasive hemodynamic monitoring devices can assess the cardiac output, preload, intrathoracic volume and tissue oxygenation which might be guide weaning management with real time inspections of responsiveness of fluid loading and vasoactive agents [6]. Patients with risk factor of ventricular dysfunction (elderly, chronic beta-blocker treatment, renal failure, pulmonary hypertension) tend to be difficult in weaning from CPB, awareness of these risk factors are important for preparing and planning aggressive cardiosupportive management earlier as prophylactic intervention [7]. Protamine sulfate is administrated slowly in order to neutralize generalized heparinization. Thromboelastography as a point-of-care monitoring device can provide rapid information about global hemostatic states (from clot formation, stabilization to fibrinolysis) to achieve goal oriented transfusions during the cardiac operation [8]. Weaning from CPB is associated with complicated problems and requires multiplinary approaches simultaneously. According to observational studies, there were strong correlations between the technical errors and teamwork disruptions caused by poor communication and lack of information during weaning period in cardiac teams [9]. The weaning moment is a critical time for confirming and verifying surgical results and achieving the optimization of hemodynamics. Thus, important information and process should be shared and fully communicated among the anesthesiologist, the cardiac surgeon, and the perfusionist.

A randomized study of coronary artery bypass surgery performed with the Resting Heart System utilizing a low vs a standard dosage of heparin

Allogeneic blood transfusion and reoperation for postoperative bleeding after the coronary artery bypass grafting have a negative impact on the patient outcome. This study aimed at evaluating the effects of reduced doses of heparin and protamine on the patient outcome, using a heparin-coated mini-cardiopulmonary bypass (CPB) system. Sixty patients undergoing elective first-time CPB were prospectively randomized either to have a reduced systemic heparinization [activated clotting time (ACT) = 250 s] or to a control group perfused with a full heparin dose (ACT = 420 s). Blood transfusions, ventilation time, early postoperative bleeding, ICU stay, reoperations for bleeding, postoperative cognitive status and the level of mobilization were registered. Twenty-nine patients were randomized to the control group, 27 patients to the low-dose group and 4 patients were excluded because of protocol violations. Four patients in the control group received a total of 10 units of packed red blood cells, and in the low-dose group, no transfusions were given, P = 0.046. No patient was reoperated because of bleeding. The ICU stay was significantly shorter in the low-dose group (8.4 vs 13.7 h, P = 0.020), less dependent on oxygen on the first postoperative day (78 vs 97%, P = 0.034), better mobilized (89 vs 59%, P = 0.006) and had less pain (visual analogue scale 2.0 vs 3.5, P = 0.019) compared with the control group. The use of a mini-CPB system combined with a low dose of heparin reduced the need for blood transfusions and may facilitate the faster mobilization of the patients.

Analysis of the Interaction between Heparin and Follistatin and Heparin and Follistatin–Ligand Complexes Using Surface Plasmon Resonance

Heparin and related heparan sulfate interact with a number of cytokines and growth factors, thereby playing an essential role in many physiological and pathophysiological processes by involving both signal transduction and the regulation of the tissue distribution of cytokines/growth factors. Follistatin (FS) is an autocrine protein with a heparin-binding motif that serves to regulate the cell proliferative activity of the paracrine hormone, and member of the TGF-β family, activin A (ActA). Follistatin is currently under investigation as an antagonist of another TGF-β family member, myostatin (Mstn), for the promotion of muscle growth in diseases associated with muscle atrophy. In this study, we employ surface plasmon resonance (SPR) spectroscopy to dissect the binding interactions between the heparin polysaccharide and both free follistatin (FS288) and its complexes (FS288-ActA and FS288-Mstn). FS288 complexes show much higher heparin binding affinity than FS288 alone. SPR solution competition studies using heparin oligosaccharides showed that the binding of FS288 and its complex to heparin is dependent on chain length. Full chain heparin or large oligosaccharides, having 18-20 sugar residues, show the highest binding activity for FS288 and the FS288-ActA complex, whereas smaller heparin molecules could interact with the FS288-Mstn complex. These interactions were also analyzed in normal physiological buffers and at different salt concentrations and pH values. Unbound follistatin was much more sensitive to all salt concentrations of >150 mM. The binding of heparin to the FS288-ActA complex was disrupted at 500 mM salt, whereas it was actually strengthened for the FS288-Mstn complex. At acidic pH values, binding of heparin to FS288 and the FS288-ActA complex was enhanced. While slightly acidic pH values (pH 6.2 and 5.2) enhanced the binding of the FS288-Mstn complex to heparin, at pH 4 heparin binding was inhibited. Overall, these studies demonstrate that binding of a specific ligand to FS288 differentially regulates its affinity and behavior for heparin molecules.

Severe Abdominal Pain as a Presenting Symptom of Probable Catastrophic Antiphospholipid Syndrome

Catastrophic antiphospholipid syndrome (APS) in pediatric medicine is rare. We report 3 adolescents who presented with acute onset of severe abdominal pain as the first manifestation of probable catastrophic APS. The 3 patients, 2 male patients and 1 female patient were 14 to 18 years old. One had been diagnosed with systemic lupus erythematosus in the past, but the other 2 had no previous relevant medical history. All presented with excruciating abdominal pain without additional symptoms. Physical examination was noncontributory. Laboratory results were remarkable for high inflammatory markers. Abdominal ultrasonography was normal, and abdominal computed tomography scan showed nonspecific findings of liver infiltration. Only computed tomography angiography revealed evidence of extensive multiorgan thrombosis. All patients had elevated titers of antiphospholipid antibodies. The patients were treated with full heparinization, high-dose steroids, and intravenous immunoglobulin with a resolution of symptoms. One patient was resistant to the treatment and was treated with rituximab. In conclusion, severe acute abdominal pain can be the first manifestation of a thromboembolic event owing to catastrophic APS even in previously healthy adolescents. Diagnosis requires a high index of suspicion with prompt evaluation and treatment to prevent severe morbidity and mortality.

P-008 Use of the axera neurovascular access device as a tool to promote patient comfort, faster recovery and turnover times without an arterial implant

PurposeVascular access is an area where little has changed in the past decade. Multiple devices currently available promise shorter patient recovery times with the use of sutures or plugs in...

An Evaluation of Factors Affecting Activated Coagulation Time

Although failure to achieve an adequate activated coagulation time (ACT) after full heparinization before cardiopulmonary bypass often is attributed to antithrombin (AT) deficiency, it remains unclear if this is a causative mechanism of decreased heparin responsiveness. Therefore, the authors determined the relationship between AT and other coagulation-related factors that affect the ACT measurement and heparin sensitivity index before the establishment of cardiopulmonary bypass. Observational study. University medical center. Adult elective cardiac surgical patients. Preoperative data collection included demographics, type of preoperative medical therapy, hemoglobin, platelet count, and AT. Intraoperative measurements included ACT and anti-Xa activity. Of the 203 patients enrolled in this study, 10% (n = 21) did not achieve an adequate ACT (≥400 seconds) after full heparinization. Subnormal AT activity (55%-79%) was not related to a low ACT and a low heparin sensitivity index. Preoperative low-molecular-weight heparin therapy did not cause a decreased ACT response. However, preoperative low hemoglobin levels and high platelet counts were associated with a decreased ACT. All these observations suggest that failure to achieve an adequate ACT is, in general, not an indicator of AT deficiency but could be affected by high platelet counts and low hemoglobin levels.

Phytohemagglutinin stimulation of lymphocytes improves mutation analysis of carbamoylphosphate synthetase 1

Carbamoylphosphate synthetase 1 (CPS1) is the first enzyme of the urea cycle. CPS1 deficiency is a rare autosomal-recessively inherited disorder that can lead to life-threatening hyperammonemia. Since there is no reliable biochemical marker for this disease, diagnosis relies on molecular means which is often done by RNA-based mutation analysis. Skin fibroblasts have been frequently used as a source of RNA while peripheral blood cells do not yield sufficient amounts of specific RNA. To avoid the costly and laborious use of cultured fibroblasts, we tried to use stimulated lymphocytes as an alternative. This was effectively achieved by short-term culture of full heparin blood in the presence of phytohemagglutinin. Hereby, subsequent reverse transcriptase-PCR of the CPS1 transcript became feasible and allowed to detect 16 different mutations (10 missense, 3 deletions, 2 nonsense, 1 duplication; 7 novel mutations) in 14 consecutive patients with CPS1 deficiency. When compared to retrospective data on cultured fibroblasts, the adapted method allowed substantial shortening of the median time to diagnosis (24days versus 122days, respectively). Besides disease causing mutations, we detected CPS1 transcript variants including one cryptic exon in RNA from lymphocytes with higher frequency than in RNA from fibroblasts. This underlines that all mutations found in RNA need to be confirmed by DNA sequencing.In conclusion, the presented approach improves the diagnostics of CPS1 deficiency. Besides the shortened time to diagnosis, the method is of particular importance for confirmation of findings of next generation sequencing and gene chips.